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Evaluation of HLA-DR Expression and T-Lymphocyte Infiltration in Osteosarcoma

1998; Elsevier BV; Volume: 194; Issue: 10 Linguagem: Inglês

10.1016/s0344-0338(98)80126-x

1618-0631

Klemens Trieb, Theresia Lechleitner, Susanna Lang, Reinhard Windhager, R. Kotz, Stephan Dirnhofer,

CAR-T cell therapy research

Although in recent years the outcome of patients with osteosarcoma has considerably been improved by com- bining neoadjuvant chemotherapy with radical surgery, there still remains the problem of nonresponse to chemotherapy. T-lymphocytes play a critical role in tumor immunology, and MHC molecules are of central importance in the regulation of the immune response. It is the aim of this study to investigate whether T-lympho- cyte infiltration of osteosarcomas and HLA-DR expres- sion on tumor cells and infiltrating immune cells are of predicitive or diagnostic value. Expression of CD3, CD8 and HLA-II was evaluated immunohistochemically on paraffin-embedded sections of 35 patients with high- grade osteosarcoma at the time of biopsy before chemotherapy and correlated with histologic response to chemotherapy, tumor size, age, alkaline-phosphatase serum levels and duration of symptoms. Thirty-four pa- tients with osteoblastoma (n = 7), osteoid osteoma (n = 7) or fibrous dysplasia (n = 20) served as controls. Osteosarcomas were infiltrated by CD3+ (33/35, 95%) and CD8+ T-lymhocytes (24/35, 68%), non malignant bone tumors by CD3+ in 91% (31/34) and CD8+ T-lympho- cytes in 74% (25/34), respectively. T-lymphocytes were positive for HLA-DR expression in 29% (10/35) in ostosarcomas and in 11% (4/34) in non-malignant con- trols. Osteosarcoma cells were positive for HLA-DR in 11/35 (31%) and non-malignant tumor cells in only 9% (3/34). Therefore, HLA-DR is overexpressed in os- teosarcoma (p < 0.05). HLA-DR expression on osteosar- coma cells showed a positive correlation with HLA-DR expression on lymphocytes (p < 0.001) as well as with duration of symptoms and age (p < 0.05). Response to preoperative chemotherapy, gender, tumor size and serum alkaline-phosphatase levels did not correlate with the expression of the molecules tested. Our results show that HLA-DR is overexpressed in osteosarcoma cells compared to non-malignant bone-tumors. This overex- pression, however, fails to serve as a predictive marker for response to neoadjuvant chemotherapy. The same is also true for tumor-infiltrating lymphocytes expressing CD3, CD8 and HLA-DR. Increased HLD-DR expres- sion in osteosarcoma is most likely due to the immune response against the tumor.